idh1 mutants r132h

GSK864是异柠檬酸脱氢酶1 (IDH1) 突变体抑制剂，对IDH1突变体R132C，R132H和R132G 有抑制作用，可用于研究心血管疾病和肿瘤疾病。

AGI-5198 (IDH-C35) 是一种选择性的突变体 IDH1R132H 抑制剂，IC50=0.07 μM。

IHMT-IDH1-053（compound 16）为高选择性不可逆IDH1R132H突变抑制剂，IC50值仅为4.7 nM。对IDH1wt和IDH2wt 突变体活性低。该化合物在IDH1R132H突变293T细胞中显著抑制2-羟基戊二酸（2-HG）生成，IC50为28 nM。IHMT-IDH1-053通过与IDH1R132H蛋白的Cys269残基形成共价键，结合至NADPH结合袋附近的变构袋。此外，它能够抑制携带IDH1R132突变的HT1080细胞系及原代AML细胞增殖。

Mutant IDH1-IN-6 is an orally active compound that effectively inhibits mutant isocitrate dehydrogenase (IDH) enzymes. It demonstrates potency and selectivity, with IC50 values of 6.27, 3.71, 36.9, and 11.5 nM for IDH1 R132H, IDH1 R132C, IDH2 R140Q, and IDH2 R172K mutants, respectively. Notably, Mutant IDH1-IN-6 exhibits lower activity in inhibiting wild-type IDH enzymes.